The main objectives of this research project are to determine the mechanisms of gene action in newly discovered immunological mutants of the mouse with emphasis on increasing the understanding of the association among immunodeficiency, autoimmunity, and lymphomagenesis. This investigation focuses ontthe mutations to motheaten (me), viable motheaten (me(v)), streaker (nu(str)) and hairless (hr). Specific studies include: analysis of stem cell function, natural killer cell activity and expression of terminal deoxynucleotidyl transferase activity in motheaten and viable motheaten mice; examination of premalignant cells in streaker mice and determination of the effect of chronological age of thymus implants on lymphomagenesis in these congenitally athymic AKR/J mice, and the effect of a remutation to hairless on the development of the immune system and lymphomagenesis in SJL/J mice.